1. Field of the Invention
The present invention relates to magnetic resonance spectroscopy (MRS), and in particular to enhancing spectral resolution of MRS and MRS imaging (MRSI) by de-convolving the effects of spatial variations in the base magnetic field (B0) determined from magnetic resonance imaging (MRI). In the following, the base magnetic field or static magnetic field may represent the combination of the external magnetic field and the macroscopic effects of the tissue susceptibility.
2. Description of the Related Art
Nuclear magnetic resonance (NMR) studies magnetic nuclei by aligning them with an applied constant magnetic field (B0) and perturbing this alignment using an alternating magnetic field (B1), orthogonal to the constant magnetic field. The resulting response to the perturbing magnetic field is the phenomenon that is exploited in magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI).
The elementary particles, neutrons and protons, composing an atomic nucleus, have the intrinsic quantum mechanical property of spin. The overall spin of the nucleus is determined by the spin quantum number I. If the number of both the protons and neutrons in a given isotope are even, then I=0. In other cases, however, the overall spin is non-zero. A non-zero spin is associated with a non-zero magnetic moment, μ, as given by Equation 1a.μ=γI  (1a)where the proportionality constant, γ, is the gyromagnetic ratio. It is this magnetic moment that is exploited in NMR. For example, nuclei that have a spin of one-half, like Hydrogen nuclei (1H), a single proton, have two possible spin states (also referred to as up and down, respectively). The energies of these states are the same. Hence the populations of the two states (i.e. number of atoms in the two states) will be approximately equal at thermal equilibrium. If a nucleus is placed in a magnetic field, however, the interaction between the nuclear magnetic moment and the external magnetic field means the two states no longer have the same energy. The energy difference between the two states is given by Equation 1b.ΔE= hγB0  (1b)where h is Plank's reduced constant. Resonant absorption will occur when electromagnetic radiation of the correct frequency to match this energy difference is applied. The energy of photons of electromagnetic radiation is given by Equation 2.E=hf  (2)where f is the frequency of the electromagnetic radiation and h=2π h. Thus, absorption will occur when the frequency is given by Equation 3.f=γB0/(2π)  (3)
The NMR frequency f is shifted by the ‘shielding’ effect of the surrounding electrons. In general, this electronic shielding reduces the magnetic field at the nucleus (which is what determines the NMR frequency). As a result, the energy gap is reduced, and the frequency required to achieve resonance is also reduced. This shift of the NMR frequency due to the chemical environment is called the chemical shift, and it explains why NMR is a direct probe of chemical structure.
Applying a short electromagnetic pulse in the radio frequency range to a set of nuclear spins simultaneously excites all the NMR transitions. In terms of the net magnetization vector, this corresponds to tilting the magnetization vector away from its equilibrium position (aligned along the external magnetic field, B0). The out-of-equilibrium magnetization vector precesses about the external magnetic field at the NMR frequency of the spins. This oscillating magnetization induces a current in a nearby pickup coil acting as a radio frequency (RF) receiver, creating an electrical signal oscillating at the NMR frequency. A portion of this time domain signal (intensity vs. time) is known as the free induction decay (FID) and contains the sum of the NMR responses from all the excited spins. In order to obtain the frequency-domain NMR spectrum (intensity vs. frequency) for magnetic resonance spectroscopy (MRS) and MRS imaging (MRSI), this time-domain signal is Fourier transformed.
Spectral resolution refers to the ability to distinguish two closely spaced peaks in any spectrum. It is one of the important criteria that define the quality of MRS and MRSI. Low spectral resolution can obscure the information available from molecules of interest, such as metabolites, in a volume of tissue, thus making difficult or impossible the detection and quantification of some or all of those metabolites.
Reduced spectral resolution is a special problem for in vivo proton MRS (1H MRS) of the brain, for several reasons. First, the chemical shift differences of different brain metabolites are relatively small (i.e, the spectral peaks are inherently very close to each other), and the line splitting caused by J-coupling further reduces the separation of the peaks in the spectrum. J-coupling (also called indirect dipole-dipole coupling) is the coupling between two nuclear spins due to the influence of bonding electrons on the magnetic field running between the two nuclei. Consequently, spectral lines of some molecules intrinsically overlap and might not be distinguished. Second, magnetic field inhomogeneity caused by the spatial variation of the static external field B0 and by local susceptibility differences of different tissues may produce linebroadening and distortion of lineshape, and thereby, reduce spectral resolution. As a result, some lines that are intrinsically separated may overlap in standard MSR measurements and can not be resolved within the portion of the spectrum associated with the metabolites. Third, motion of the person being imaged may produce linebroadening and reduce spectral resolution.
Many techniques have been developed to improve the spectral resolution of in vivo MRS. These techniques can be classified into two categories representing either acquisition or processing of the spectral data.
Within the category of data acquisition, the most commonly employed strategy for improving spectral resolution is the automated techniques for improving the homogeneity of the magnetic field B0. Fast and high order shimming techniques have been implemented on modern scanners to make B0 more uniform across a subject being scanned, yet these methods cannot eliminate all variation in local magnetic fields that are caused by the differing magnetic susceptibilities of various interposed tissues within the body. To image at higher magnetic field strengths is another strategy to increase spectral resolution, as well as the signal-to-noise ratio (SNR) of the MRS. Theoretically, doubling the field strength should double the differences in chemical shifts and the separations peaks in the metabolic spectrum. Unfortunately, the observed benefit of higher field strengths in improving spectral resolution is much lower than theoretically predicted. For example, spectral resolution at 3 Tesla (T, 1 T=1 Newton per Ampere per meter) only increases marginally compared with spectral resolution obtained at 1.5 T. Two reasons for this are that scanners with higher field strengths come with greater inhomogeneity of their magnetic fields, and the higher fields shorten the T2 relaxation times of metabolites, both of which increase linewidths of the spectrum. The T2 relaxation time is the time for precessing nuclei to fall out of alignment with each other (returning the net magnetization vector to a non-precessing field) and thus stop producing a signal. In addition, the upper limit on field strength is constrained by practical and safety considerations. Techniques of fast acquisition of data can reduce the total scan time and thereby reduce the likelihood that the person being imaged moves, and this will indirectly reduce the linebroadening caused by subject motion. Other acquisition-based techniques that are designed to improve spectral resolution include higher spatial resolution MRSI and 2 dimensional (2D) J-resolved MRSI. However, both of these techniques usually require long scan times which cannot be afforded in many clinical and research applications.
Most processing methods to improve spectral resolution are either borrowed or modified from those commonly used in processing conventional Nuclear Magnetic Resonance (NMR), but these usually produce very limited improvements of spectral resolution for data acquired in vivo. The method of Positive Exponential Multiplication (PEM), for example, multiplies the free induction decay (FID, defined above) with a positive exponential function. Although this operation can increase the spectral resolution, it also increases noise in the signal and reduces its overall SNR. This is a price that usually cannot be afforded with the in vivo data, because the SNR of in vivo MRS is typically already very low. A method similar to PEM is the double exponential multiplication (DEM), which transforms the Lorentzian lineshape to a Gaussian lineshape, which has a narrower linewidth at the bottom of a peak than the former does. With carefully selected exponential factors, DEM can improve spectral resolution while largely preserving the SNR. Because the lineshape of in vivo MRS is more Gaussian than Lorentzian, however, DEM has limited applicability for in vivo MRSI. Another processing-based method is the spectral de-convolution using the isolated singlet of water as a reference. An assumption of this approach is that the water peak and metabolic peaks have an identical lineshape, which is not always true for in vivo MRSI due at least to two reasons: 1] the differences in distribution profiles; and 2] the chemical shift artifacts. Moreover, acquiring an MRSI for water doubles the total MRSI scan time (about 30 minutes per scan), which cannot be afforded in many clinical and research applications. Because of these inherent difficulties, the existing processing-based methods have limited applicability for improving spectral resolution in MRSI in vivo.